Although high-calorie fast foods and soft drinks are easily available, and people spend more time participating in sedentary activities such as watching television or using a computer, these factors are insufficient to explain the huge increase in obesity observed during the 20th century. The often overlooked obesogenic chemicals likely play an important role in the obesity and diabetes pandemic. Studies dating back to the 1970s have shown that low-dose chemical exposures were associated with weight gain in experimental animals 1. Since then, a growing number of studies show links between toxins and weight gain, obesity and diabetes. Known or suspected culprits behind negative epigenetic changes include toxins such as heavy metals, pesticides, plastic compounds including BPA, diesel exhaust, tobacco smoke, polycyclic aromatic hydrocarbons, hormones, radioactivity, viruses, bacteria and endocrine-disrupting chemicals.
The main role of fat cells is to store energy and release it when needed. Scientists now know that fat tissue acts as an endocrine organ, releasing hormones related to appetite and metabolism. Research to date suggests that different obesogenic compounds may have different mechanisms of action, some affecting the number of fat cells, others the size of fat cells, and still others the hormones that affect appetite, satiety, food preferences, and energy metabolism. Another mechanism through which these chemical obesogens can contribute to weight gain is through their impact on the gut microbiome, linking gut ecology and environmental chemicals to obesity and diabetes 2.
BPA, or bisphenol A, is a chemical found in everything from plastic bottles to metal food containers may be partly to blame for excess weight. BPA has been shown to alter the body’s metabolism, increasing weight gain and making it difficult to lose weight. A number of studies have reported elevated levels of BPA in obese and overweight individuals 3. BPA levels have been related to obesity in US studies 4,5 and in the Chinese population 6. In both American and Chinese schoolchildren, urinary BPA levels were associated with BMI 7-11. In a study of 1,326 children, girls between ages nine and 12 with high BPA levels had double the risk of being obese compared to girls with low BPA levels, validating previous animal and human studies. The chemical can alter the body’s metabolism and make it harder to lose weight. Girls with high levels of BPA—two micrograms per liter or more—were two times more likely to be obese than girls with lower levels of BPA in the same age group. Girls with very high levels of BPA, more than 10 micrograms per liter, were five times more likely to be obese, the study shows 12. Urinary BPA in pregnant women was related to BMI in their offspring at four years of age 13. Similar results were found in girls aged nine years 14. The oestrogenic properties of bisphenol A (BPA) have been known since 1936 15.
BPA has been shown to induce obesity in rodents in experimental settings 16,17. In animal experiments, mothers’ exposure to BPA is producing the same outcomes that we see in humans born light at birth: an increase in abdominal fat and glucose intolerance. BPA was seen to affect rodent fat cells at very low doses—1,000 times below the dose that regulatory agencies presume causes no effect in humans, whereas at higher doses researchers saw no effect. Hormone receptors typically respond to very low levels of hormone, so it makes sense that they may be activated by low levels of an endocrine mimic, whereas high levels of a chemical may actually cause receptors to shut down altogether, preventing any further response 18.
Children exposed to certain chemicals, POPs (Persistent Organic Pollutants), in the womb have a higher risk of being overweight. POPs include a wide variety of long-lasting chemicals that collect in fat and accumulate in wildlife and people. Some were made as pesticides, such as DDT, and others as electrical insulators including polychlorinated biphenyls (PCBs). POPs can also act as endocrine disruptors and disrupt hormone function. The developing foetus is exposed to POPs passed from the mother through the placenta.
Several longitudinal birth cohort studies have examined how prenatal exposure to DDT (now banned in most countries) and DDE affects child growth. Positive associations between prenatal DDT and DDE exposure and body mass index and overweight status have been reported in birth cohorts in Europe 19 and in the United States 20,21. In a study of 344 children, both PCB and DDE exposure led to an increased risk of weight gain in children. The link between being overweight and PCB and DDE levels in cord blood was stronger in girls than boys. DDT was associated with weight gain only in boys, especially in children with average or above average fat intakes. In some cases, children with higher POPs exposure were almost twice as likely to be overweight compared to children with lower exposure, depending on the pollutant and gender 20. In a study of 6,770 subjects aged six to 19 years, a dose-dependent increase in obesity was observed in the groups with highest urinary concentrations of 2,5-dichlorophenol (2,5-DCP) and reported a possible relationship between exposure to 2,5-DCP and obesity in children 22.
A growing body of evidence demonstrates that the use of certain organophosphate pesticides may also be associated with weight gain and diabetes risk 23.
Similar results of POPs have been found in animal experiments. Mice fed high-fat diets gained about 30% more weight and experienced raised blood sugar, compared to other mice eating the same high-fat diets, when they also ingested doses of a brominated flame retardant, hexabromocyclododecane (HBCD), which is used in building materials and insulation. It accumulates in the tissues of animals and humans, and previous animal studies have shown that it may disrupt hormones, metabolism and immune systems. Some evidence, mostly with lab animals, suggests that prenatal exposure to these obesogens can reprogram metabolism, leading to more fat cells and raising the risk of obesity later in life. The mice, which on average weighed 21 grams, were fed a high-fat diet with a high dose of flame retardant and gained an average of 21 grams. Mice fed the same diet without the chemical gained about 16 grams. That means that mice fed the extra flame retardant doubled their weight and put on around 25% more weight than the control group, and also had higher blood sugar and higher insulin levels than the unexposed mice. Their livers also weighed more and their adipose tissues were inflamed. Changes were also noted in the gene expression of their glucose transporters 24 HBCD is still used in large volumes.
Perfluorooctanoic acid (PFOA) is a ubiquitous chemical, used in nonstick cookware, Gore-Tex™ waterproof clothing, Scotchgard™ stain repellent on carpeting and mattresses; it is a potential endocrine disruptor. When pregnant mice were given PFOA during pregnancy, their offspring became obese in adulthood, reaching significantly higher weight levels than controls. Exposed offspring also had elevated levels of leptin, a hormone secreted by adipose tissue that affects appetite and metabolism.
Pre- and postnatal exposure to Firemaster®550 (FM550) has been associated with increased anxiety, obesity, and early-onset puberty in rats. Researchers reported further evidence that components of FM550 may act as environmental obesogens, stimulating adipogenesis (fat formation) at the expense of bone health. House dust in the US contains high levels of organophosphate flame-retardants, and their metabolites are ubiquitous in human urine. The authors estimated that young children could ingest 120 μg/day TPP from indoor exposure to dust alone.
Phthalates are plasticizers that also have been related to obesity in humans and occur in many PVC items, as well as in scented items such as air fresheners, laundry products, personal care products and many plastics. Studies suggest that phthalates have significant effects on obesity, especially after prenatal exposure at low doses (BMI) in children and adults 25.
In early studies, tributyltin (TBT), commonly found in home anti-mould and dust mite treatments, was given to pregnant mice and resulted in heavier offspring; even if the offspring eat normal food, they get slightly fatter. Tributyltin can exert toxicity through multiple mechanisms but most recently has been shown to bind, activate, and mediate gene regulation central to lipid metabolism and adipocyte biology. In support of this, long-term obesogenic effects on whole body adipose tissue are also reported 26. In another animal experiment, exposure to TBT for 45 days resulted in obesity and hepatic steatosis and induced the occurrence of insulin and leptin resistance 27.
Arsenic in drinking water has been found to promote a number of diseases that may stem from dysfunctional adipose lipid and glucose metabolism. Arsenic inhibits adipocyte differentiation and promotes insulin resistance; it also alters gene signaling for aberrant lipid storage and metabolism that may contribute to the pathogenesis of metabolic disease caused by environmental arsenic exposures 28. Similarly, a study of environmental contaminants in 114 seven- to nine-year-old Flemish children found a negative association between cadmium and abdominal and subcutaneous fat 29.
In a study of hypertensive rats, researchers found that short-term exposure to air pollution, over a 10-week period, elevates blood pressure in rats already predisposed to the condition 30. Another animal study from the same group found that early exposure to ultrafine particulates led to the accumulation of abdominal fat and insulin resistance in mice even if they ate a normal diet 30. The study compared mice fed a high-fat diet with those fed a normal, healthy diet, and exposed some members of both groups daily to ultrafine particulate matter, controlling for all other factors. In the end, all of the mice exposed to air pollution, including those fed a normal diet, had increased abdominal and subcutaneous fat. These findings suggest that fine particulate pollution exposure alone, in the presence of a normal diet, may lead to an increase in fat cell size and number, and also have a proinflammatory effect.
Experimental results also suggest a high-fat diet may exacerbate the health effects of inhaled PM2.5; this means obese people may be at increased risk. Mice breathing PM2.5 and eating a high-fat diet developed IR, systemic inflammation, and increased abdominal fat, compared with mice eating the same diet but breathing filtered air 31. This mechanism directly ties a known inflammatory mechanism in the pathogenesis of type 2 diabetes to exposure to environmental air pollution; the inflammatory damage likely creates a vicious cycle that can also contribute to cardiovascular disease and obesity. In addition, studies have recently reported that small increases in urban ambient PM2.5 can decrease insulin sensitivity in healthy subjects 32, suggesting that PM2.5 may contribute to metabolic syndrome and to the progression from metabolic syndrome to diabetes.
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